Safety and Efficacy of Insulin Degludec/Liraglutide (IDegLira) and Insulin Glargine U100/Lixisenatide (iGlarLixi), Two Novel Co-Formulations of a Basal Insulin and a Glucagon-Like Peptide-1 Receptor Agonist, in Patients With Diabetes Not Adequately Controlled on Oral Antidiabetic Medications

Abstract

Novel co-formulations of basal insulin analogs and glucagon-like peptide-1 (GLP-1) receptor agonists have provided new options for patients with type 2 diabetes who are not reaching recommended glycemic targets. The components of currently available co-formulations (insulin degludec/ liraglutide [IDegLira,] and insulin glargine U100/lixisenatide [iGlarLixi]) act synergistically to address multiple pathophysiologic defects while minimizing the side effects associated with either component when used alone. In Europe, these products are approved for use in patients on regimens of one or more oral antidiabetic drugs; in the United States, they are indicated for use as an adjunct to diet and exercise in patients with type 2 diabetes inadequately controlled with either basal insulin or their respective GLP-1 receptor agonist component. This article reviews key clinical trials in which these products were initiated in insulin-naive patients and describes how they can be safely and effectively titrated in clinical practice.

Superior HbA1c control with the fixed‐ratio combination of insulin degludec and liraglutide (IDegLira) compared with a maximum dose of 50 units of insulin degludec in Japanese individuals with type 2 diabetes in a phase 3, double‐blind, randomized trial

“…Treatment effect on body weight was consistent with previous findings, a review of which may be found in Wysham et al 2018 and Aroda et al 2018, and demonstrates that the benefits of IDegLira extend beyond glycaemic control. The initial weight loss observed in both treatment groups may be the result of the decrease in insulin dose from pre‐trial doses of approximately 28 U to starting doses of 10 dose steps/U, or up to 16 dose steps/U in some cases .…”

“…Despite this, the rates of severe or BG-confirmed hypoglycaemia were similar between groups. The difference in HbA1c levels observed with IDegLira was achieved at a significantly lower insulin dose than the dose of degludec, supporting a clinically significant contribution of the liraglutide component to overall glycaemic control.Treatment effect on body weight was consistent with previous findings,[15][16][17][18][19] a review of which may be found inWysham et al 2018 andAroda et al 2018, 20,21 and demonstrates that the benefits of IDegLira extend beyond glycaemic control. The initial weight loss observed in both treatment groups may be the result of the decrease in insulin dose from pre-trial doses of approximately 28 U to starting doses of 10 dose steps/U, or up to 16 dose steps/U in some cases 22.…”

Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update

“…Therefore, timely addition of insulin should be considered to protect pancreatic β-cells from gluco-lipotoxicity and exploit anabolic effects on musculature. As a consequence, flexible fixed ratio combinations of insulins with a GLP-1RA have been developed: insulin glargine/lixisenatide (iGlarLixi [ 134 ]) and insulin degludec/liraglutide (iDegLira [ 135 ]). With these fixed-ratio combinations, pen applications that require only one injection per day have been provided.…”

Titratable fixed-ratio combination of insulin glargine plus lixisenatide: A simplified approach to glycemic control in type 2 diabetes mellitus

“…In LixiLan-L and LixiLan-O, iGlarLixi has shown superior reductions in HbA1c relative to its individual components, and in LixiLan-G has also proven to be a useful and more effective therapy in patients failing on GLP-1 RA [12]. Furthermore, post-hoc analyses, systematic reviews, meta-analyses and real-world studies confirmed the feasibility, efficacy and safety of iGlarLixi in treatment of patients with T2DM [18,29,31,32,34,35,40,41,43,44,47,56]. The results obtained with iGlarLixi were achieved regardless of diabetes duration, even in patients with T2DM for >15 years, and its benefits are likely to occur independently of the integrity of beta-cell function [33,35].…”

“…Randomized controlled clinical studies were carried out to assess the efficacy and safety of iGlarLixi [31].…”